Mechanism of virus-induced stimulation of the hypothalamus-pituitary-adrenal axis.

Increased blood levels of glucocorticoids are observed during certain viral infections. In this paper, we report data obtained from a model in rodents showing that the pituitary-adrenal axis is stimulated following inoculation of Newcastle Disease Virus (NDV). No evidence for an ectopic, lymphoid source of ACTH-like immunoreactive material capable of inducing this effect was obtained. Administration of virus-free supernatants from cocultures of human peripheral blood leukocytes with NDV also stimulated ACTH and glucocorticoid output in normal mice. This observation showed the immunological cell origin of the mediator of the hormonal effect. Pretreatment of the supernatant with anti-IL-1 sera neutralized its capacity to induce an increase in glucocorticoid and ACTH levels in blood. Furthermore, injection of IL-1 in nanogram amounts also increased ACTH and glucocorticoid blood levels. Thus, we conclude that IL-1 is the most likely mediator of the stimulation of the pituitary-adrenal axis during viral infection. The reported data are also discussed in the general context of the postulated glucocorticoid-associated immunoregulatory circuit.